title: Enhanced uridine bioavailability following administration of a triacetyluridine-rich nutritional supplement.
abstract: BACKGROUND
  Uridine is a therapy for hereditary orotic aciduria and is being investigated in other disorders caused by mitochondrial dysfunction, including toxicities resulting from treatment with nucleoside reverse transcriptase inhibitors in HIV. Historically, the use of uridine as a therapeutic agent has been limited by poor bioavailability. A food supplement containing nucleosides, NucleomaxX®, has been reported to raise plasma uridine to supraphysiologic levels.
  
  
  RESULTS
  Single- and multi-dose PK studies following NucleomaxX® were compared to single-dose PK studies of equimolar doses of pure uridine in healthy human volunteers. Product analysis documented that more than 90% of the nucleoside component of NucleomaxX® is in the form of triacetyluridine (TAU). Single and repeated dosing with NucleomaxX® resulted in peak plasma uridine concentrations 1-2 hours later of 150.9 ± 39.3 µM and 161.4 ± 31.5 µM, respectively, levels known to ameliorate mitochondrial toxicity in vitro. C(max) and AUC were four-fold higher after a single dose of NucleomaxX® than after uridine. No adverse effects of either treatment were observed.
  
  
  CONCLUSIONS
  NucleomaxX®, containing predominantly TAU, has significantly greater bioavailability than pure uridine in human subjects and may be useful in the management of mitochondrial toxicity.
authors.affiliation: University of California San Francisco, San Francisco, California, United States of America. melissa.weinberg@gmail.com
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Weinberg
authors.forename: Mark C
authors.initials: MC
authors.lastname: Roman
authors.forename: Peyton
authors.initials: P
authors.lastname: Jacob
authors.forename: Michael
authors.initials: M
authors.lastname: Wen
authors.forename: Polly
authors.initials: P
authors.lastname: Cheung
authors.forename: Ulrich A
authors.initials: UA
authors.lastname: Walker
authors.forename: Kathleen
authors.initials: K
authors.lastname: Mulligan
authors.forename: Morris
authors.initials: M
authors.lastname: Schambelan
mesh_terms: D000085:Acetates; D000328:Adult; D001682:Biological Availability; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009994:Osmolar Concentration; D015854:Up-Regulation / Q000187:drug effects; D014529:Uridine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D055815:Young Adult
chemical_list: D000085:Acetates; C000609666:uridine triacetate; D014529:Uridine